The aim of this application is to develop the candidate's knowledge and skills in patient-oriented clinical research in the domain of neurodevelopmental disorders. Toward this aim, he will complete a program including formal coursework, mentored training, and a research project on the molecular genetics and psychophysiology of social anxiety in children with fragile X syndrome and the fragile X premutation. The research project includes measurement of biobehavioral markers of autonomic and amygdala function, fragile X mental retardation 1 (FMR1) mRNA and gene expression, and behavioral measures in children with fragile X and matched comparison samples of children with idiopathic developmental disability and typical development. The primary underlying hypothesis of the project is that the FMR1 mutation causes over-responsiveness of the amygdala to social stimuli, leading to symptoms of social anxiety and avoidance that are hallmark behavioral features of the fragile X behavioral phenotype. The study will also investigate whether this mechanism of increased anxiety contributes to autistic behaviors, particularly deficits in reciprocal social behavior, in children with fragile X. The candidate's ultimate goals are to become a clinical researcher able to compete for independent grant support, and to conduct high quality studies that will directly lead to improvement in the lives of individuals with fragile X, as well as to contribute to a better understanding of the genetic and physiological mechanisms underlying emotional and behavioral disturbance in children with neurodevelopmental disorders. By the end of the award period, the candidate will become a recognized clinical researcher in the area of neurodevelopmental disorders, and will receive funding to conduct research as an independent investigator.